Lumasiran Sodium (Monograph)

Drug class: Other Miscellaneous Therapeutic Agents

Medically reviewed by Drugs.com on Dec 17, 2023. Written by ASHP.

Introduction

Small interfering ribonucleic acid (siRNA) that targets hydroxyacid oxidase 1 (HAO1).

Uses for Lumasiran Sodium

Primary Hyperoxaluria Type 1

Used for treatment of primary hyperoxaluria type 1 (PH1) in adult and pediatric patients to lower urinary and plasma oxalate levels.

Has been designated an orphan drug by FDA for treatment of PH1.

European guidelines on the management of primary hyperoxaluria generally recommend lumasiran and other RNA interfering agents as second-line treatment of PH1 in select patients following conservative management with hyperhydration, potassium citrate, and pyridoxine supplementation.

Lumasiran Sodium Dosage and Administration

Administration

Sub-Q Administration

Administer by sub-Q injection by a healthcare professional. Commercially available as a ready-to-use solution in a single-dose vial that does not require reconstitution or dilution before administration.

When preparing for administration, divide injection volumes equally into multiple syringes if >1.5 mL. Use sterile 0.3-mL syringes for volumes <0.3 mL. If using a 0.3 mL insulin syringe for administration, 1-unit markings indicate 0.01 mL.

Administer sub-Q into the abdomen, thigh, or the side or back of the upper arms; avoid administration into scar tissue, inflamed or swollen areas, or around the area of the navel. Rotate injection sites and separate each injection site by at least 2 cm if more than 1 injection is required for a single dose. Following administration, discard any unused portion of the drug.

If a dose is missed, administer as soon as possible; resume monthly or quarterly dosing from the time of the most recently administered dose.

Dosage

Available as lumasiran sodium; dosage expressed in terms of lumasiran.

Pediatric Patients

Primary Hyperoxaluria Type 1

Sub-Q

Administer as 3 monthly loading doses followed by maintenance doses starting 1 month after the last loading dose. Dosing regimen is based on actual body weight (see Table 1).

Adults

Primary Hyperoxaluria Type 1

Sub-Q

Administer as 3 monthly loading doses followed by maintenance doses starting 1 month after the last loading dose.

Dosing regimen is based on actual body weight (See Table 1).

Special Populations

Hepatic Impairment

No dosage adjustment recommended in patients with mild (total bilirubin >ULN to 1.5 times the ULN or AST above the ULN) or moderate (total bilirubin >1.5–3 times the ULN with any AST) hepatic impairment.

Not studied in patients with severe (total bilirubin >3 times the ULN with any AST) hepatic impairment.

Renal Impairment

Dosage adjustment not necessary in patients with renal impairment, including patients treated with hemodialysis.

In patients receiving hemodialysis, administer after dialysis if given on dialysis days. Not studied in patients on peritoneal dialysis.

Geriatric Patients

No specific dosage recommendations.

Cautions for Lumasiran Sodium

Contraindications

• None.

Warnings/Precautions

Immunogenicity

Anti-drug antibodies (ADA) detected; no clinically significant differences in safety, pharmacokinetics, or pharmacodynamics of lumasiran in patients who tested positive for ADA.

Specific Populations

Pregnancy

No data available to assess risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes with use of lumasiran in pregnancy.

Lactation

Not known whether drug or its metabolites are distributed into human milk; effects on breast-fed infants or on production of milk also unknown. Consider developmental and health benefits of breastfeeding with the mother's need for lumasiran and any potential adverse reactions on the breast-fed child from the drug or underlying maternal condition.

Pediatric Use

Safety and efficacy established in pediatric patients from birth.

Geriatric Use

Not known whether geriatric patients respond differently than younger patients due to insufficient numbers of patients ≥65 years of age in clinical trials.

Hepatic Impairment

No clinically significant differences in lumasiran pharmacokinetics/pharmacodynamics in patients with mild or moderate hepatic impairment; effect of severe hepatic impairment unknown.

Renal Impairment

No clinically significant differences in lumasiran pharmacokinetics/pharmacodynamics in patients with renal impairment or on hemodialysis; safety and efficacy not established in patients receiving peritoneal dialysis.

Common Adverse Effects

Most common adverse reaction (≥20%) is injection site reactions.

Drug Interactions

No drug interaction studies conducted. Lumasiran is not a substrate, inhibitor, or inducer of CYP enzymes and does not modulate the activities of drug transporters.

Specific Drugs

Lumasiran Sodium Pharmacokinetics

Absorption

Bioavailability

Approximately dose-proportional increases in plasma exposure following single sub-Q doses of 0.3–6 mg/kg.

Time-dependent pharmacokinetics with multiple doses of 1 and 3 mg/kg once monthly or 3 mg/kg every 3 months.

Does not accumulate in plasma after repeated monthly or quarterly administration.

Onset

Time to maximum concentration ranges from 0.5–12 hours with a median of 4 hours.

Special Populations

Maximum concentration was higher in children weighing <20 kg due to high loading doses and fast absorption rate.

When administered at the recommended dose, the AUC was similar across body weights ranging from 6.2–110 kg.

Distribution

Extent

Not known whether lumasiran distributes into breast milk.

Plasma Protein Binding

85%

Elimination

Metabolism

Conversion to oligonucleotides by endonucleases or exonucleases.

Elimination Route

Dose is primarily excreted as inactive metabolite, with <26% excreted unchanged into urine within 24 hours.

Half-life

5.2 hours

Stability

Storage

Parenteral

Injection, for subcutaneous administration

Store in original container at 2–25°C until ready for use.

Actions

• Liver-directed RNA interfering agent that targets hydroxyacid oxidase 1 mRNA, silencing the gene that encodes glycolate oxidase.

• As a result, reduces oxalate synthesis by reducing the amount of glycolate oxidase available for hepatic oxalate production.

• Not expected to be effective in patients with primary hyperoxaluria (PH)2 or PH3; mechanism of action does not affect the same metabolic pathways leading to PH2 or PH3.

Advice to Patients

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Advise women to inform their clinician if they are or plan to become pregnant or plan to breast-feed.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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